1. Field of the Invention
For many clinical uses, it is desirable to employ monoclonal antibodies which will not be recognized as foreign by the host. Particularly, where repeated administration of monoclonal antibodies to the host is envisioned, the host is likely to be sensitized and to make antibodies that inactivate xenogeneic monoclonal antibodies and thus vitiate their beneficial effects. Despite the importance of having human monoclonal antibodies available, obtaining such antibodies has proven to be difficult. The human.times.human crosses occur with relatively low efficiency so that obtaining monoclonal antibodies has proven to be difficult, particularly where the crosses have been with peripheral blood lymphocytes, a convenient source of human B-lymphocytes.
It would therefore be desirable to have malignant fusion partner cell lines capable of being fused at high efficiency with human B-lymphocytes and which do not introduce into the nutrient medium immunoglobulin chains xenogeneic to humans.
2. Description of the Prior Art
EPO 0 044 722 describes a mutant myeloma cell line which, after fusion with antigen-sensitized human spleen B-lymphocytes, yielded monoclonal antibody-secreting human-human hybridomas. Croce et al., Nature (1980) 288:488-489 describe a human lymphoblastoid cell line that also yielded antibody-secreting human-human hybridomas. However, the frequency with which such hybridomas are obtained after fusing these and other tested human cell lines with human B-lymphocytes is undesirably low. Many mouse myeloma cell lines are available, some of which, when fused with mouse B-lymphocytes, consistently give a very high yield of mouse antibody-secreting mouse-mouse hybridomas. This suggested that mouse myeloma cell lines could be fused successfully with human B-lymphocytes to generate mouse-human heterohybridomas secreting human monoclonal antibodies. Although such fusions were first reported ten years ago (Schwaber and Cohen, Nature (1973) 244:444-447) and have in rare instances yielded stable human monoclonal antibody-producing hybridomas (Schlom et al., PNAS USA (1980) 77:6841-6845), this approach has suffered from the fact that human chromosomes are selectively and usually totally eliminated from human-mouse hybrids, thus leading, after a variable but usually brief time interval, to the loss of those human chromosomes (#2, 14, and 22) on which reside the genes for the heavy and light chains of immunoglobulin (the generic class of molecule to which all antibodies belong), and thus to the cessation of human monoclonal antibody production. It is thus clear that the development of methods and cell lines whereby these and other essential human chromosomes are retained in mouse-human heterohybridomas would make this a practical and efficient approach to human monoclonal antibody production.